A combination of a microemulsion and a phospholipid complex for topical delivery of oxymatrine

Abstract

Oxymatrine (OMT), a water-soluble drug, has a very low oral bioavailability because of its low membrane permeability and its biotransformation in the gastrointestinal tract. Formulated as an oxymatrine-phospholipid complex (OMT-PLC) can improve the lipid solubility and effectiveness of OMT. The purpose of this study was to explore the utility of the combination of a microemulsion and an OMT-PLC as a topical delivery vehicle for enhancing the absorption and efficacy of OMT. The solubility of OMT-PLC was determined and phase diagrams of microemulsions were constructed. Various microemulsion formulations were developed and characterized by their physicochemical properties, and their in vitro and in vivo permeability through skin. An optimal microemulsion (ME4), which presented as spherical droplets and consisted of 10.0% OMT-PLC, 8.0% isopropyl myristate, 30.0% Cremophor RH40/polyethylene glycol 400 (1:1) and 52.0% water, was selected. It possessed an average droplet size of 32.4 nm, a low viscosity of 113.7 mPa · s, and a high cloud point of 88°C. Compared to the control solution, ME4 provided better skin permeability in vitro and a higher retention ratio of OMT in skin in vivo. Moreover, ME4 significantly enhanced the antiproliferative activity of OMT on scar fibroblasts. These results indicate that the combination of a microemulsion and a phospholipid complex represents an effective vehicle for topical delivery of OMT.

Kinetic Analysis of the Toxicity of Pharmaceutical Excipients Cremophor EL and RH40 on Endothelial and Epithelial Cells

“…Double bonds are more reactive than single covalent bonds in general, and may result in higher cytotoxic effect. In addition, the hydrophilic-lipophilic balance value of Cremophor EL (12)(13)(14) is lower than that of RH40 (14)(15)(16). The higher lipophilicity of Cremophor EL may cause higher perturbation in cell membranes.…”

In Vitro, Ex Vivo, and In Vivo Evaluation of the Effect of Saturated Fat Acid Chain Length on the Transdermal Behavior of Ibuprofen-Loaded Microemulsions

“…Mice were sacrificed at predetermined intervals (1, 2, 3, 4, 6, 8, 12, and 24 h) after treatment. Subsequently, the specific treated skin areas were stripped, washed with PBS (pH 7.4) extensively, and cut into pieces and extracted using 1 mL methanol for 1 h. The supernatant was filtered, centrifuged and analyzed by HPLC to test the drug retention ratio in skin …”

“…Therefore, we firstly classified eight saturated FAs into three groups based on the chain length shown as below: (1) were saturated LFAs—isopropyl palmitate (IPP), isopropyl myristate (IPM), and methyl myristate; (2) medium‐chain FAs (MFA)—Imwitor® 312, Imwitor® 742, and Labrafaclipoible WL 1349®; (3) short‐chain FAs (SFA)—tributyrin and triacetin . In addition, Cremophor RH40, a nonionic surfactant with a good emulsification capacity and P‐gp and cytochrome P modulating ability, was selected as the surfactant in this study . Transcutol P was chosen as the cosurfactant in the ME formulation because of its nonirritating and nonvolatile capacities compared with that of ethanol .…”

“…16 In addition, Cremophor RH40, a nonionic surfactant with a good emulsification capacity and P-gp and cytochrome P modulating ability, 17 was selected as the surfactant in this study. 18 Transcutol P was chosen as the cosurfactant in the ME formulation because of its nonirritating and nonvolatile capacities compared with that of ethanol. [19][20][21] IBU, a well-known Biopharmaceutics Classification System (BCS) II drug was selected as the hydrophobic model drug in our study because of its small molecular weight (MW = 206) and relatively high octanol-water partition coefficient (log P = 4).…”

Oxymatrine inhibited cell proliferation by inducing apoptosis in human lung cancer A549 cells

“…Sophora flavescens Ait is a traditional Chinese medicine, and it has been used for the treatment for thousands of years [5,6]. Oxymatrine (OM), is a kind of alkaloid components found in the roots of sophora species, had been reported to have many pharmacological effects, such as anti-inflammation, anti-virus, anti-fibrotic, anti-allergic and protecting hepatocytes and cardiovascular [7][8][9].…”